Win Time In Favor of Treatment (WINFT) for Hierarchical Endpoints

Sahil S. Patel; Huiman Barnhart; Lu Mao; Roland A. Matsouaka; Yuliya Lokhnygina

Home/Archive/arXiv

arXiv · 2608.08835

Win Time In Favor of Treatment (WINFT) for Hierarchical Endpoints

Sahil S. Patel·Huiman Barnhart·Lu Mao·Roland A. Matsouaka·Yuliya Lokhnygina

View original source ↗Read source document ↗Export metadata ↓

Abstract

Standard win statistics methods determine a win, loss, or tie for a pair of subjects based on their worst outcomes (up to the end of study) that may not fully utilize all patients' conditions or disease experience throughout the follow-up period. While the newly developed win-time statistics fully utilize all patients' longitudinal information, these statistics have been limited to time-to-event endpoints and require monotonic pattern of the events. As such, they are not applicable to any type nor number of hierarchical longitudinal endpoints. We propose the win time in favor of treatment (WINFT), a general measure for any hierarchical longitudinal endpoints, that summarizes the total time a subject in the treatment group spends in a more favorable health state than a subject in the control group. Unlike existing win time methods, the WINFT does not require the component outcomes to be monotone and does not rely on modeling assumptions for estimating state probabilities. This flexibility allows analysis of a complex and diverse set of endpoints, and includes existing win time methods as special cases. Moreover, the WINFT is estimated based on U-statistics, which provide direct framework for variance estimation and confidence interval derivation, under independent censoring and missing at random assumptions, without expensive bootstrapping. We examine the performance of the proposed WINFT estimation method through simulation studies, and illustrate the method using data from the ACTT-1 COVID-19 and HF-ACTION trials. Overall, the WINFT offers a flexible and interpretable estimand for assessing treatment in clinical trial data with complex longitudinal outcomes.

Explore related subjects

stat.ME

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Sahil S. Patel, Huiman Barnhart, Lu Mao, Roland A. Matsouaka, Yuliya Lokhnygina. 2026-08-09. Win Time In Favor of Treatment (WINFT) for Hierarchical Endpoints. https://arxiv.org/abs/2608.08835

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

A Bayesian Framework for Multivariate Differential Analysis

Differential analysis is a routine procedure in the statistical analysis toolbox across many applied fields, including quantitative proteomics, the main illustration of the present paper. The state-of-the-art limma approach uses a hierarchical formulation with moderated-variance estimators for each analyte directly injected into the t-statistic. While standard hypothesis testing strategies are recognised for their low computational cost, allowing for quick extraction of the most differential among thousands of elements, they generally overlook key aspects such as handling missing values, inter-element correlations, and uncertainty quantification. The present paper proposes a fully Bayesian framework for differential analysis, leveraging a conjugate hierarchical formulation for both the mean and the variance. Inference is performed by computing the posterior distribution of compared experimental conditions and sampling from the distribution of differences. This approach provides well-calibrated uncertainty quantification at a similar computational cost as hypothesis testing by leveraging closed-form equations. Furthermore, a natural extension enables multivariate differential analysis that accounts for possible inter-element correlations. We also demonstrate that, in this Bayesian treatment, missing data should generally be ignored in univariate settings, and further derive a tailored approximation that handles multiple imputation for the multivariate setting. We argue that probabilistic statements in terms of effect size and associated uncertainty are better suited to practical decision-making. Therefore, we finally propose simple and intuitive inference criteria, such as the overlap coefficient, which express group similarity as a probability rather than traditional, and often misleading, p-values.

stat.ME↗

arXiv2026

Interpretable Deep Neural Network for Modeling Functional Surrogates

Developing surrogates for computer models has become increasingly important for addressing complex problems in science and engineering. This article introduces an artificial intelligent (AI) surrogate, referred to as the DeepSurrogate, for analyzing functional outputs with vector-valued inputs. The relationship between the functional output and vector-valued input is modeled as an infinite sequence of unknown functions, each representing the relationship at a specific location within the functional domain. These spatially indexed functions are expressed through a combination of basis functions and their corresponding coefficient functions, both of which are modeled using deep neural networks (DNN). The proposed framework accounts for spatial dependencies across locations, while capturing the relationship between the functional output and scalar predictors. It also integrates a Monte Carlo (MC) dropout strategy to quantify prediction uncertainty, enhancing explainability in the deep neural network architecture. The proposed method enables efficient inference on datasets with approximately 50,000 spatial locations and 20 simulations, achieving results in under 10 minutes using standard hardware. The approach is validated on extensive synthetic datasets and a large-scale simulation from the Sea Lake and Overland Surge from Hurricanes (SLOSH) simulator. An open-source Python package implementing the method is made available.

stat.ME↗

arXiv2026

Bayesian inference for the learning rate in Generalised Bayesian inference

In Generalised Bayesian Inference (GBI), the learning rate and hyperparameters of the loss must be estimated. These inference-hyperparameters can't be estimated jointly with the other parameters, from the data, by giving them a prior. However, in some settings there exist unknown ``true'' hyperparameter-values about which it is meaningful to have prior belief. It is then possible to use Bayesian inference with held-out data to get hyperparameter-posteriors. We define two hyperparameter posteriors, one based on an Expected Log Pointwise Predictive Density (ELPPD)-utility and one aiming to cover the pseudo-true parameter. The new framework supports estimation and uncertainty quantification for multiple hyperparameters jointly. Experiments show that the resulting GBI-posteriors outperform Bayesian inference on simulated test data and select optimal or near-optimal hyperparameter values in a large real problem of text analysis. Generalised Bayesian inference is particularly useful for combining multiple data sets and most of our examples belong to that setting. We also give asymptotic results for some of the special ``multi-modular'' Generalised Bayes posteriors which we use in our examples.

stat.ME↗